In recent years, there have been a growing number of patients suffering from lifestyle-related diseases, especially such as diabetes and hyperlipidemia, as the eating habit of Japanese people is increasingly Westernized and they have less tendency to take exercise than did before. Diabetes and hyperlipidemia are known as critically basal diseases that could cause the development of arteriosclerosis and lead to ischemic heart diseases as a result.
Diabetes are classified into type I (insulin-dependent diabetes mellitus, IDDM) and type II (non-insulin-dependent diabetes mellitus, NIDDM). Sufferers of the latter type account for more than 90 percent of diabetic patients. In many cases, type II diabetes is complicated by hyperlipidemia. So that most patients with such a complicated type II diabetics often develop arteriosclerosis and subsequently ischemic heart diseases. Recent large-scale clinical studies have shown that the risks of these diseases are remarkably reduced by means of a therapy for lowering blood glucose, as well as by means of a therapy for lowering blood lipid (particularly, a therapy for effectively lowering blood triglyceride (hereinafter referred to as “blood TG”)) (SENDCAP study (Diabetes Care (US), American Diabetes Association, 21, 641-648 (1998)); and DAIS study (Lancet (UK), Lancet, 357, 905-910 (2001))).
For example, the results of the DAIS study show that, when fenofibrate, which is known as a blood lipid lowering agent, is orally administered to diabetic patients complicated with hyperlipidemia in which a blood glucose level is sufficiently controlled, a decrease in average minimum lumen diameter and an increase in constriction degree, which indicate coronary artery lesion, are significantly suppressed, and a decrease in average lumen diameter, which indicates diffuse change, is significantly suppressed. The results also show a significant decrease in the number of deaths that were assumed to result from progress of coronary artery diseases, or a significant decrease in the occurrence of cardiovascular events. The above results show that sufficient control of blood glucose level and blood lipid is effective for treatment of patients with both type II diabetes and hyperlipidemia (the number of such patients has increased in recent years), and for prevention of arteriosclerosis and ischemic heart diseases resulting from arteriosclerosis, which are often developed by such patients. However, fenofibrate per se is well known to exhibit insufficient effect of lowering the blood glucose level of a diabetic patient. Therefore, demand has arisen for a drug exhibiting a high blood lipid lowering effect as well as a blood glucose lowering effect, which drug can be used as means for effectively treating patients with both type II diabetes and hyperlipidemia, and as means for preventing arteriosclerosis and ischemic heart diseases resulting from arteriosclerosis, which are developed by such patients.
Meanwhile, suppression of lowering of blood free fatty acid (hereinafter referred to as “blood FFA”) has been reported to implicate insulin resistance (Khan, et al., Diabetologia (Germany), European Association for Study of Diabetes., 39 (Suppl), A53 (1996)).
Aminopropionic acid derivatives having a phenyloxazole structure have been reported as compounds exhibiting a blood lipid lowering effect as well as a blood glucose lowering effect (WO 96/38415, WO 97/31907, and WO 2000/08002).
Adiponectin, which is secreted from human adipose cells to the body, has been known to exhibit the effect of improving insulin resistance, which is a cause of type II diabetes.